PMID- 29462686
OWN - NLM
STAT- MEDLINE
DCOM- 20180907
LR  - 20181202
IS  - 1873-3476 (Electronic)
IS  - 0378-5173 (Linking)
VI  - 541
IP  - 1-2
DP  - 2018 Apr 25
TI  - PLGA nanoformulation of sparfloxacin enhanced antibacterial activity with 
      photoprotective potential under ambient UV-R exposure.
PG  - 173-187
LID - S0378-5173(18)30109-1 [pii]
LID - 10.1016/j.ijpharm.2018.02.028 [doi]
AB  - Sparfloxacin (SPFX) is a broad spectrum antibiotic which inhibits bacterial DNA 
      gyrase enzyme activity. However, photodegradation in the presence of UVA limits 
      its antibacterial activity and induces phototoxicity. Thus, to encounter this 
      problem, we have developed poly d,l-lactic-co-glycolic acid (PLGA) loaded SPFX 
      nanoparticles. Here, we have performed a comparative antibacterial activity of 
      SPFX and its nanoparticles (NPs) through molecular docking and plate sensitivity 
      assay. Under environmental UVA exposure, photoexcited SPFX significantly 
      generates ROS, DNA damage and mitochondrial mediated cell death in comparison to 
      PLGA-SPFX-NPs (nano SPFX) in human skin cell line (HaCaT). In presence of UVA, 
      bulk SPFX induced cell cycle arrest with appearance of sub-G1 peak showing 
      apoptosis while nano SPFX did not show any change. SPFX triggered apoptosis via 
      alteration in membrane integrity of mitochondria and lysosome in comparison to 
      PLGA-SPFX-NPs. Involvement of mitochondrial mediated cell death was confirmed by 
      down-regulation of anti-apoptotic Bcl-2 and procaspase-3 and upregulation of 
      pro-apoptotic Bax, cytochrome-c and caspase-3 proteins expression. Specific 
      caspase inhibitor, Z-VAD-FMK showed involvement of caspase cascade pathway in 
      apoptosis. Our finding suggests that controlled release of SPFX from 
      PLGA-SPFX-NPs can reduce its side effects and enhance its antibacterial activity. 
      Thus, nanotization of fluoroquinolones will be a significant step to reduce the 
      problem of resistance and phototoxicity of this group.
CI  - Copyright (c) 2018 Elsevier B.V. All rights reserved.
FAU - Singh, Jyoti
AU  - Singh J
AD  - Photobiology Laboratory, Systems Toxicology and Health Risk Assessment Group, 
      CSIR-Indian Institute of Toxicology Research (CSIR-IITR), Vishvigyan Bhavan, 31, 
      Mahatma Gandhi Marg, Lucknow 226001, Uttar Pradesh, India; Academy of Scientific 
      and Innovative Research (AcSIR), CSIR-IITR Campus, Lucknow 226001, Uttar Pradesh, 
      India.
FAU - Dwivedi, Ashish
AU  - Dwivedi A
AD  - Photobiology Laboratory, Systems Toxicology and Health Risk Assessment Group, 
      CSIR-Indian Institute of Toxicology Research (CSIR-IITR), Vishvigyan Bhavan, 31, 
      Mahatma Gandhi Marg, Lucknow 226001, Uttar Pradesh, India; Pineal Research Lab, 
      Department of Zoology, Banaras Hindu University, Varanasi, Uttar Pradesh 221005, 
      India.
FAU - Ray, Lipika
AU  - Ray L
AD  - Pharmaceutics Division, CSIR-Central Drug Research Institute (CSIR-CDRI), Sector 
      10, Sitapur Road, Jankipuram Extension, Lucknow, Uttar Pradesh 226031, India.
FAU - Chopra, Deepti
AU  - Chopra D
AD  - Photobiology Laboratory, Systems Toxicology and Health Risk Assessment Group, 
      CSIR-Indian Institute of Toxicology Research (CSIR-IITR), Vishvigyan Bhavan, 31, 
      Mahatma Gandhi Marg, Lucknow 226001, Uttar Pradesh, India; School of Dental 
      Sciences, Department of Biochemistry, Babu Banarasi Das University, BBD City, 
      Faizabad Road, Lucknow 226028, Uttar Pradesh, India.
FAU - Dubey, Divya
AU  - Dubey D
AD  - Photobiology Laboratory, Systems Toxicology and Health Risk Assessment Group, 
      CSIR-Indian Institute of Toxicology Research (CSIR-IITR), Vishvigyan Bhavan, 31, 
      Mahatma Gandhi Marg, Lucknow 226001, Uttar Pradesh, India; School of Dental 
      Sciences, Department of Biochemistry, Babu Banarasi Das University, BBD City, 
      Faizabad Road, Lucknow 226028, Uttar Pradesh, India.
FAU - Srivastva, Ajeet K
AU  - Srivastva AK
AD  - Photobiology Laboratory, Systems Toxicology and Health Risk Assessment Group, 
      CSIR-Indian Institute of Toxicology Research (CSIR-IITR), Vishvigyan Bhavan, 31, 
      Mahatma Gandhi Marg, Lucknow 226001, Uttar Pradesh, India; School of Dental 
      Sciences, Department of Biochemistry, Babu Banarasi Das University, BBD City, 
      Faizabad Road, Lucknow 226028, Uttar Pradesh, India.
FAU - Kumari, Smita
AU  - Kumari S
AD  - Photobiology Laboratory, Systems Toxicology and Health Risk Assessment Group, 
      CSIR-Indian Institute of Toxicology Research (CSIR-IITR), Vishvigyan Bhavan, 31, 
      Mahatma Gandhi Marg, Lucknow 226001, Uttar Pradesh, India; Environmental 
      Biotechnology Laboratory, CSIR-Indian Institute of Toxicology Research 
      (CSIR-IITR), Vishvigyan Bhavan, 31, Mahatma Gandhi Marg, Lucknow 226001, Uttar 
      Pradesh, India.
FAU - Yadav, Randhir Kumar
AU  - Yadav RK
AD  - Pineal Research Lab, Department of Zoology, Banaras Hindu University, Varanasi, 
      Uttar Pradesh 221005, India.
FAU - Amar, Saroj Kumar
AU  - Amar SK
AD  - Forensic Science, School of Bioengineering and Biosciences, Lovely Professional 
      University, Punjab, India.
FAU - Haldar, Chandana
AU  - Haldar C
AD  - Pineal Research Lab, Department of Zoology, Banaras Hindu University, Varanasi, 
      Uttar Pradesh 221005, India.
FAU - Ray, Ratan Singh
AU  - Ray RS
AD  - Photobiology Laboratory, Systems Toxicology and Health Risk Assessment Group, 
      CSIR-Indian Institute of Toxicology Research (CSIR-IITR), Vishvigyan Bhavan, 31, 
      Mahatma Gandhi Marg, Lucknow 226001, Uttar Pradesh, India; Academy of Scientific 
      and Innovative Research (AcSIR), CSIR-IITR Campus, Lucknow 226001, Uttar Pradesh, 
      India. Electronic address: rsray@iitr.res.in.
LA  - eng
PT  - Journal Article
DEP - 20180217
PL  - Netherlands
TA  - Int J Pharm
JT  - International journal of pharmaceutics
JID - 7804127
RN  - 0 (Anti-Bacterial Agents)
RN  - 0 (Drug Carriers)
RN  - 0 (Fluoroquinolones)
RN  - 0 (Reactive Oxygen Species)
RN  - 1SIA8062RS (Polylactic Acid-Polyglycolic Acid Copolymer)
RN  - 26009-03-0 (Polyglycolic Acid)
RN  - 33X04XA5AT (Lactic Acid)
RN  - Q90AGA787L (sparfloxacin)
SB  - IM
EIN - Int J Pharm. 2018 Oct 25;550(1-2):488-489. PMID: 30143247
EIN - Int J Pharm. 2019 Sep 10;568:118515. PMID: 31331687
MH  - Anti-Bacterial Agents/chemistry/*pharmacology
MH  - Apoptosis/drug effects
MH  - Cell Cycle Checkpoints/drug effects
MH  - Cell Line
MH  - DNA Damage/drug effects
MH  - Drug Carriers/chemistry
MH  - Drug Compounding/*methods
MH  - Drug Stability
MH  - Fluoroquinolones/chemistry/*pharmacology
MH  - Humans
MH  - Keratinocytes
MH  - Lactic Acid/*chemistry
MH  - Mitochondria/drug effects/metabolism
MH  - Molecular Docking Simulation
MH  - Molecular Structure
MH  - Nanoparticles/chemistry
MH  - Photolysis/*radiation effects
MH  - Polyglycolic Acid/*chemistry
MH  - Polylactic Acid-Polyglycolic Acid Copolymer
MH  - Reactive Oxygen Species/metabolism
MH  - Ultraviolet Rays/adverse effects
OTO - NOTNLM
OT  - Apoptosis
OT  - DNA damage
OT  - DNA gyrase
OT  - Photostability
OT  - Sparfloxacin
EDAT- 2018/02/21 06:00
MHDA- 2018/09/08 06:00
CRDT- 2018/02/21 06:00
PHST- 2017/12/26 00:00 [received]
PHST- 2018/01/30 00:00 [revised]
PHST- 2018/02/16 00:00 [accepted]
PHST- 2018/02/21 06:00 [pubmed]
PHST- 2018/09/08 06:00 [medline]
PHST- 2018/02/21 06:00 [entrez]
AID - S0378-5173(18)30109-1 [pii]
AID - 10.1016/j.ijpharm.2018.02.028 [doi]
PST - ppublish
SO  - Int J Pharm. 2018 Apr 25;541(1-2):173-187. doi: 10.1016/j.ijpharm.2018.02.028. 
      Epub 2018 Feb 17.